Osteoarthritis (hereinafter sometimes referred to as “OA”) is the most common disease among patients with joint diseases in which major lesions are damage to and/or degeneration of articular cartilage. Among the present medication for the OA disease, an analgesic and antiinflammatory agent or a hyaluronic acid preparation is used as a symptomatic treatment to alleviate pain, but satisfactory effects are not achieved, and thus the patient finally reaches a condition in which surgical treatment is necessary.
It is considered that articular cartilage is a tissue deficient in ability for regeneration. As examples of the development of a therapy for restoring articular cartilage in the OA disease, a method for removing articular chondrocytes from a body, culturing the cells in vitro, and implanting the proliferated cells in the damaged articular site is known. However, this method requires a surgical operation and has many problems, and thus is not established as a useful therapy (Onstott A. T. et al., AORN J., 71, 843–845, 848–851, 2000). Further, an attempt to use several physiologically active substances exhibiting a differentiation inducing activity for chondrocytes as a therapeutic agent is carried out. However, the effect of this is now being evaluated in an animal model in which articular cartilage is artificially damaged, and the attempt has not reached the stage of clinical application (Sellers R. S. et al., J. Bone Joint Surg. Am., 79A, 1452–1463, 1997; and Trippel S. B., J. Rheumatol. Suppl., 43, 129–132, 1995).
Blood vessels, nerves, and lymph ducts do not exist in a cartilage tissue. Articular cartilage is composed of chondrocytes, and an extracellular matrix produced by the chondrocytes. The extracellular matrix such as type II collagen or proteoglycan produced by articular chondrocytes gives a specific elasticity and strength and a resistance against pressure to the cartilage tissue, and then plays an important role in functioning as articular cartilage (Huber M. et al., Investigative Radiology, 35(10), 573–580, 2000). However, in the OA disease, degeneration of the articular cartilage tissue or fibrocartilage formation occurs. In particular, type II collagen is decomposed, and thus the amount of type II collagen, which normally functions significantly, decreases [Hollander A. P. et al., J. Clin. Invest., 93(4), 1722–1732, 1994].
Similarly to type II collagen, aggrecan is produced by articular chondrocytes and a major proteoglycan forming the cartilaginous tissue. Aggrecan plays an important role in carrying out a function as articular cartilage, but a decomposition and degeneration of aggrecan are observed in the OA disease [Neame P. J. et al., J. Fla. Med. Assoc., 81(3), 191–193, 1994].